Bottom Line:
During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg.Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy.No new safety signals were reported.

Background/aims: This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD).

Methods: Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored.

Results: Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 µg/mL (160/80 mg group) and 7.5-9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups.

Conclusions: Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.

Figure 4: Clinical remission, clinical response, and CDAI over time. Percentages of patients in remission (CDAI <150) over time (A). Percentages of patients achieving CR-70 (decrease from baseline CDAI of ≥70 points) over time (B). Percentages of patients achieving CR-100 (decrease from baseline CDAI of ≥100 points) over time (C). Error bars represent 95% CI. Non-responder imputation was used for data analysis.

Mentions:
Clinically relevant remission and response were observed as early as week 2 and were sustained to week 26 (Fig. 4A–C). Numerically higher remission rates were observed in the 160/80 mg group as early as week 2 (47%) compared to that in the 80/40 mg group (27%), and this trend was sustained at all time points through week 8 (Fig. 4A). At week 2, CR-70 and CR-100 rates were higher in the 160/80 mg group than in the 80/40 mg group, and similar rates were observed through week 26 (Fig. 4B, C). Week 4 remission rates in subgroups based on baseline variables are shown in Supplementary Table 1. Due to small numbers of patients in some strata, conclusions are difficult to draw.

Figure 4: Clinical remission, clinical response, and CDAI over time. Percentages of patients in remission (CDAI <150) over time (A). Percentages of patients achieving CR-70 (decrease from baseline CDAI of ≥70 points) over time (B). Percentages of patients achieving CR-100 (decrease from baseline CDAI of ≥100 points) over time (C). Error bars represent 95% CI. Non-responder imputation was used for data analysis.

Mentions:
Clinically relevant remission and response were observed as early as week 2 and were sustained to week 26 (Fig. 4A–C). Numerically higher remission rates were observed in the 160/80 mg group as early as week 2 (47%) compared to that in the 80/40 mg group (27%), and this trend was sustained at all time points through week 8 (Fig. 4A). At week 2, CR-70 and CR-100 rates were higher in the 160/80 mg group than in the 80/40 mg group, and similar rates were observed through week 26 (Fig. 4B, C). Week 4 remission rates in subgroups based on baseline variables are shown in Supplementary Table 1. Due to small numbers of patients in some strata, conclusions are difficult to draw.

Bottom Line:
During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg.Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy.No new safety signals were reported.

Background/aims: This was a Phase 2 study (NCT02015793) to evaluate the pharmacokinetics, safety, and efficacy of adalimumab in Chinese patients with Crohn's disease (CD).

Methods: Thirty, adult Chinese patients with CD (CD Activity Index [CDAI] 220-450; high-sensitivity [hs]-C-reactive protein [CRP] ≥3 mg/L) received double-blind adalimumab 160/80 mg or 80/40 mg at weeks 0/2, followed by 40 mg at weeks 4 and 6. An open-label extension period occurred from weeks 8-26; patients received 40 mg adalimumab every other week. Serum adalimumab concentration and change from baseline in fecal calprotectin (FC) were measured during the double-blind period. Clinical remission (CDAI <150), response (decrease in CDAI ≥70 points from baseline), and change from baseline in hs-CRP were assessed through week 26. Nonresponder imputation was used for missing categorical data and last observation carried forward for missing hs-CRP/FC values. No formal hypothesis was tested. Adverse events were monitored.

Results: Mean adalimumab serum concentrations during the induction phase were 13.9-18.1 µg/mL (160/80 mg group) and 7.5-9.5 µg/mL (80/40 mg group). During the double-blind period, higher remission/response rates and greater reductions from baseline in hs-CRP and FC were observed with adalimumab 160/80 mg compared to that with 80/40 mg. Adverse event rates were similar among all treatment groups.

Conclusions: Adalimumab serum concentrations in Chinese patients with CD were comparable to those observed previously in Western and Japanese patients. Clinically meaningful remission rates and improvement in inflammatory markers were achieved with both dosing regimens; changes occurred rapidly with adalimumab 160/80 mg induction therapy. No new safety signals were reported.